Review Articles in 2007

High mobility group A (HMGA) proteins alter chromatin structure and therefore affect the transcription of large sets of genes. This can contribute to both benign and malignant disease in several ways.

Mutations inBRCA1 and BRCA2are associated with cancer risk. However, it is important to understand the differences between populations, as both the prevalence of the mutations and the nature of their effects can differ between groups.

CHK2, an important player in the DNA-damage response signalling pathway, is a candidate multiorgan tumour susceptibility gene. Will the targeted modulation of this kinase or exploitation of its loss in tumours prove to be an effective anti-cancer strategy?

Centrosomes have a crucial role in the formation of bipolar mitotic spindles, which are essential for accurate chromosome segregation. Certain oncogenic and tumour-suppressor proteins control centrosome duplication and function. How does their mutation result in numeral and functional centrosome abnormalities?

How can image-guided radiotherapy be used to optimize radiotherapy doses to the tumour while sparing sensitive surrounding healthy tissue?

Cancer dormancy is a very important yet poorly understood phenomenon in cancer progression. What do we know about the mechanisms of cancer dormancy and can it be targeted therapeutically?

Fox proteins are transcriptional regulators of many biological processes. The authors discuss how these proteins are deregulated in cancer and the roles they have in both tumorigenesis and cancer progression.

Mixed lineage leukaemia (MLL) has histone methyltransferase activity and regulates the expression of genes such as Hox genes. This activity is lost in MLL fusion proteins resulting from inter-chromosomal translocations, which are leukemogenic. How do MLL fusions function and what is their role in leukaemia stem cells?

Studying metastasis has been difficult because until recently only the end result (metastases) could be observed. Advances in imaging technology have enabled us to begin to unravel the steps of metastasisin vivo.

Fatty acid synthase (FASN) catalyses the synthesis of fatty acids, and this synthetic pathway is upregulated in many tumours. How might FASN and increased lipogenesis be involved in cancer, and is FASN a valid therapeutic target?

Approximately 25% of lung cancer cases worldwide are not attributable to smoking, accounting for over 300,000 deaths each year. What do we know about this unique but poorly characterized disease?

Mantle cell lymphoma, characterized by proliferation of mature B lymphocytes, is one of the most aggressive lymphomas. What molecular pathways are involved in its pathogenesis, and how can these be exploited to predict patient prognosis and design new therapies?

Breast cancer is not a single disease, but is instead a collection of diseases that have distinct histopathological features, genetic and genomic variability, and diverse prognostic outcomes. What is the most powerful way to investigate this heterogeneous disease?

The myeloproliferative disorders (MPD) polycythaemia vera (PV), essential thombocythaemia (ET), and primary myelofibrosis (PMF) are clonal disorders of multipotent haematopoietic progenitors, and most patients with these diseases acquire a single point mutation in the cytoplasmic tyrosine kinase JAK2 (JAK2V617F). What are the implications of these findings for MPD?

Animal models of cancer are an immense resource for cancer medicine, but only now are we realising their full potential. What new approaches are needed to derive the maximum value for cancer patients from mouse models of cancer?

Accumulating evidence indicates that the active metabolite of vitamin D, 1α,25(OH)₂D₃, or vitamin D analogues might have potential as anticancer agents because their administration has antiproliferative effects, can activate apoptotic pathways and inhibit angiogenesis. What are the possibilities for 1α,25(OH)₂D₃and vitamin D analogues as preventative and therapeutic anticancer agents?

Alcohol is one of the most widely consumed toxic substances, and approxmiately 3.6% of cancers result from chronic alcohol drinking. What are some of the mechanisms by which alcohol acts as a carcinogen?

Multiple myeloma is an incurable B-cell malignancy that is actively sustained by the bone marrow microenvironment. Targeting myeloma cells and their bone marrow interactions seems a promising strategy to overcome drug resistance and improve patient outcome.

Cisplatin was first used for cancer therapy in the 1970s. Interest in platinum drugs has been revived recently: new agents have been developed, a better understanding of resistance mechanisms has been gained, and combination trials with resistance modulators and targeted agents have been initiated.

Altered expression of specific Ca²⁺ channels and pumps are characterizing features of some cancers. The ability of Ca²⁺ to regulate both cell death and proliferation, combined with the potential for pharmacological modulation, offers the opportunity for a set of new drug targets in cancer. Which Ca²⁺channels and pumps should be targeted and what strategy should be used?